Cyclic AMP, ATP, and Reversed Anaphylactic Histamine Release from Rat Mast Cells

Abstract

Reversed anaphylactic histamine release by rabbit (Rab) anti-Rat Fab was independent of serum factors and was established as being noncytolytic in that challenged isolated mast cells still retained incorporated ⁴²K and excluded trypan blue dye after releasing histamine. The release reaction involved the activation of a diisopropyl fluorophosphate (DFP)-sensitive esterase and required energy utilization. Prostaglandin E₁ (PGE₁) consistently produced a dose-related increase in the mast cell content of cyclic 3′,5′-adenosine monophosphate (cyclic AMP) which at the optimal concentration was 2 to 3 times the average baseline of 4.71 pmoles/10⁶ mast cells (range -1 to 10 pmoles/10⁶ mast cells). Aminophylline and PGE₁ alone each inhibited Rab anti-Rat Fab-induced histamine release with concomitant increases in cyclic AMP, and the combination of these agents had a synergistic effect on both parameters. The inhibition of histamine release by the endogenous accumulation of cyclic AMP was reproduced by the exogenous administration of dibutyryl cyclic AMP. The interaction of Rab anti-Rat Fab with isolated mast cells resulted in a depletion of the cellular levels of cyclic AMP, ATP, and calcium in association with histamine release. Although these consequences of membrane perturbation may be unrelated, it seems more likely that they are interrelated and intrinsic to reversed anaphylactic histamine release.